Distinct membrane-permeabilizing interactions of an antiviral alkyl glucoside detergent: Comparison with Triton X-100 and SDS.

As sustainable sugar-based surfactants, alkyl glycosides (AGs) like undecyl glucoside (SL-11W) are promising candidates to replace antiviral detergents such as Triton X-100 (TX-100). While SL-11W and TX-100 have been reported to similarly inactivate membrane-enveloped viruses, the molecular mechanisms by which AGs such as SL-11W disrupt phospholipid membranes remain unclear. Herein, we investigated the membrane-disruptive behaviors of SL-11W alongside TX-100 and sodium dodecyl sulfate (SDS) as reference detergents and identified distinct mechanistic features of SL-11W. Dye release experiments showed that all three detergents permeabilized fluid-phase, zwitterionic lipid vesicles mainly above their respective critical micelle concentration (CMC) values while dynamic light scattering (DLS) and quartz crystal microbalance-dissipation (QCM-D) measurements revealed different interaction behaviors. SDS and TX-100 exhibited solubilizing activities, including micellization and/or extensive vesicle disruption, whereas SL-11W did not solubilize membranes and instead promoted vesicle remodeling without micellization. Laurdan fluorescence measurements further indicated that SDS disrupted interfacial packing, TX-100 had weaker destabilizing effects, and SL-11W did not cause interfacial destabilization. In addition, we examined how membrane curvature modulates SL-11W activity, with interaction outcomes shifting from modest remodeling in larger vesicles (>100 nm) to instability in highly curved vesicles (∼50 nm). Based on these results and the absence of micellization, we discuss how SL-11W permeabilizes membranes through a strain-mediated remodeling pathway and consider factors such as alkyl chain insertion and interfacial interactions associated with its glucose headgroup. Collectively, these findings support that SL-11W exhibits a distinct mechanism of membrane permeabilization compared to classical detergents with irreversible solubilizing activity.